EP3697303B1 - Transkutane tragbare vorrichtung zur kontinuierlichen überwachung von biomarkern im blut - Google Patents
Transkutane tragbare vorrichtung zur kontinuierlichen überwachung von biomarkern im blut Download PDFInfo
- Publication number
- EP3697303B1 EP3697303B1 EP18903032.3A EP18903032A EP3697303B1 EP 3697303 B1 EP3697303 B1 EP 3697303B1 EP 18903032 A EP18903032 A EP 18903032A EP 3697303 B1 EP3697303 B1 EP 3697303B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- sensor
- electrodes
- wells
- impedance
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000012544 monitoring process Methods 0.000 title claims description 35
- 210000004369 blood Anatomy 0.000 title description 26
- 239000008280 blood Substances 0.000 title description 26
- 239000000090 biomarker Substances 0.000 title description 18
- 239000012491 analyte Substances 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 45
- 238000003780 insertion Methods 0.000 claims description 35
- 230000004044 response Effects 0.000 claims description 32
- 230000037431 insertion Effects 0.000 claims description 31
- 230000027455 binding Effects 0.000 claims description 23
- 239000012212 insulator Substances 0.000 claims description 22
- 239000000758 substrate Substances 0.000 claims description 22
- 238000001514 detection method Methods 0.000 claims description 20
- 239000012528 membrane Substances 0.000 claims description 18
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 14
- 239000011241 protective layer Substances 0.000 claims description 14
- 239000010931 gold Substances 0.000 claims description 12
- 229910052737 gold Inorganic materials 0.000 claims description 12
- 238000011065 in-situ storage Methods 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 56
- 229910021389 graphene Inorganic materials 0.000 description 56
- 102000004169 proteins and genes Human genes 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 41
- 239000010410 layer Substances 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 32
- 239000000523 sample Substances 0.000 description 32
- 239000011148 porous material Substances 0.000 description 30
- 102000004127 Cytokines Human genes 0.000 description 27
- 108090000695 Cytokines Proteins 0.000 description 27
- 210000002966 serum Anatomy 0.000 description 25
- 210000003491 skin Anatomy 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 230000006870 function Effects 0.000 description 22
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 21
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 21
- 238000005259 measurement Methods 0.000 description 20
- 238000012360 testing method Methods 0.000 description 18
- 230000008569 process Effects 0.000 description 17
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 16
- 230000035945 sensitivity Effects 0.000 description 15
- 239000000427 antigen Substances 0.000 description 14
- 108091007433 antigens Proteins 0.000 description 14
- 102000036639 antigens Human genes 0.000 description 14
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 229940039781 leptin Drugs 0.000 description 12
- 239000013642 negative control Substances 0.000 description 12
- 229920001223 polyethylene glycol Polymers 0.000 description 12
- 230000009871 nonspecific binding Effects 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 230000002757 inflammatory effect Effects 0.000 description 9
- 235000012239 silicon dioxide Nutrition 0.000 description 9
- 102000016267 Leptin Human genes 0.000 description 8
- 108010092277 Leptin Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 238000000231 atomic layer deposition Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 8
- 238000001179 sorption measurement Methods 0.000 description 8
- 230000009870 specific binding Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 238000013459 approach Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 102000004388 Interleukin-4 Human genes 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000004926 polymethyl methacrylate Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000002123 temporal effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000000954 titration curve Methods 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 4
- 108090000176 Interleukin-13 Proteins 0.000 description 4
- 102000003816 Interleukin-13 Human genes 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 238000000206 photolithography Methods 0.000 description 4
- 229920001690 polydopamine Polymers 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 108091023037 Aptamer Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009713 electroplating Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 238000002847 impedance measurement Methods 0.000 description 3
- 238000001566 impedance spectroscopy Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 238000003368 label free method Methods 0.000 description 3
- 238000011898 label-free detection Methods 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 238000000059 patterning Methods 0.000 description 3
- 238000001020 plasma etching Methods 0.000 description 3
- 229920000052 poly(p-xylylene) Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000011897 real-time detection Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000012706 support-vector machine Methods 0.000 description 3
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 2
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000013145 classification model Methods 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000000708 deep reactive-ion etching Methods 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000000157 electrochemical-induced impedance spectroscopy Methods 0.000 description 2
- 238000000609 electron-beam lithography Methods 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000002032 lab-on-a-chip Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 239000006225 natural substrate Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000002161 passivation Methods 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 229920000307 polymer substrate Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000000992 sputter etching Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- IPVYMXZYXFFDGW-UHFFFAOYSA-N 1-methylpiperidin-4-ol;hydrochloride Chemical compound Cl.CN1CCC(O)CC1 IPVYMXZYXFFDGW-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000013875 Heart injury Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 1
- 101150085950 IL10 gene Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 239000007772 electrode material Substances 0.000 description 1
- 238000000572 ellipsometry Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000001453 impedance spectrum Methods 0.000 description 1
- 238000012623 in vivo measurement Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003960 inflammatory cascade Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000010801 machine learning Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000010309 melting process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000001465 metallisation Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002110 nanocone Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002071 nanotube Substances 0.000 description 1
- 239000002070 nanowire Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 239000000107 tumor biomarker Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000004832 voltammetry Methods 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/053—Measuring electrical impedance or conductance of a portion of the body
- A61B5/0538—Measuring electrical impedance or conductance of a portion of the body invasively, e.g. using a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14503—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
- A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
- A61B5/685—Microneedles
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/02—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0636—Integrated biosensor, microarrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0645—Electrodes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
- B01L2300/123—Flexible; Elastomeric
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Medical Informatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Analytical Chemistry (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Biotechnology (AREA)
- Clinical Laboratory Science (AREA)
- Electrochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
Claims (15)
- Sensor (10, 110, 510) zum Nachweis eines Zielanalyten in einer Probe, wobei der Sensor Folgendes umfasst:a) ein Paar von leitenden Elektroden (12, 14, 112, 114, 512, 514), wobei die Elektroden durch einen Spalt getrennt sind;b) einen Isolator (18, 118, 518), der in dem Spalt zwischen den Elektroden angeordnet ist; undc) mehrere Vertiefungen (20, 120, 520), die in einer regelmäßig beabstandeten Anordnung (22, 122, 522) angeordnet sind, die durch eine der Elektroden (12, 112, 512) und den Isolator definiert ist, um die andere der Elektroden (14, 114, 514) freizulegen, wobei die Vertiefungen zum Aufnehmen einer Probe, die einen Zielanalyten enthält, konfiguriert sind, wobei eine Impedanz zwischen den Elektroden durch den Zielanalyten moduliert wird, wenn er in der Probe, die in den Vertiefungen aufgenommen wird, vorliegt, wobei die modulierte Impedanz mit einer angelegten elektrischen Spannung messbar ist, wobei die modulierte Impedanz indikativ für die Konzentration des Zielanalyten in der Probe ist.
- Sensor nach Anspruch 1, wobei die Vertiefungen zum Binden des Zielanalyten konfiguriert sind und wobei die Vertiefungen wahlweise Antikörper immobilisiert im Inneren der Vertiefungen enthalten, um den Zielanalyten zu binden.
- Sensor nach Anspruch 1, wobei die Elektroden parallele Platten sind oder wobei die Elektroden überlappen, um eine überlappende Region zu bilden, wobei die Vertiefungen innerhalb der überlappenden Region definiert sind, oder wobei die Elektroden Goldelektroden sind und der Isolator Aluminiumoxid umfasst.
- Sensor nach Anspruch 1, wobei die Elektroden und der Isolator auf einem Substrat (28, 128, 428, 528) hergestellt sind und wobei die Elektrode, welche die Vertiefungen definiert, mit einer Schutzschicht (30, 130, 425, 530) bedeckt ist.
- Sensor nach Anspruch 4, wobei das Substrat flexibel ist oder wobei die Schutzschicht (425) Abschnitte der Vertiefungen bedeckt und zum sequentiellen Offenlegen der Abschnitte der Vertiefungen zur kontinuierlichen Überwachung des Analyten konfiguriert ist.
- Sensor nach Anspruch 1, wobei der Durchmesser jeder Vertiefung im Bereich von etwa 20 Nanometer bis etwa 4 Mikrometern liegt.
- Sensor nach Anspruch 1, welcher ferner eine Schaltung (32) beinhaltet, die an die Elektroden gekoppelt ist, wobei die Schaltung über die Elektroden die elektrische Spannung an die Probe in den Vertiefungen anlegt und über die Elektroden einen Strom als Reaktion auf die angelegte Spannung misst, wobei die modulierte Impedanz zwischen den Elektroden als eine Funktion der angelegten Spannung und des gemessenen Stroms bestimmt wird.
- Sensor nach Anspruch 7, wobei die Schaltung einen Lock-In-Verstärker beinhaltet oder wobei die Schaltung zum Anlegen der Spannung als ein zeitveränderliches Signal konfiguriert ist und wobei die modulierte Impedanz bei einer Frequenz im Bereich von etwa 50 kHz bis etwa 10 MHz bestimmt wird und wobei die modulierte Impedanz wahlweise bei etwa 1 MHz bestimmt wird.
- Verfahren zum markierungsfreien Abtasten eines Zielanalyten in einer Probe, wobei das Verfahren Folgendes umfasst:a) Bereitstellen eines Sensors (10, 110, 510), welcher Folgendes umfasst:i) ein Paar von leitenden Elektroden (12, 14, 112, 114, 512, 514), wobei die Elektroden durch einen Spalt getrennt sind;ii) einen Isolator (18, 118, 518), der in dem Spalt zwischen den Elektroden angeordnet ist; undiii) mehrere Vertiefungen (20, 120, 520), die in einer regelmäßig beabstandeten Anordnung (22, 122, 522) angeordnet sind, die durch eine der Elektroden (12, 112, 512) und den Isolator definiert ist, um die andere der Elektroden (14, 114, 514) freizulegen;b) Aufnehmen einer Probe in mindestens einem Abschnitt der Vertiefungen; undc) Messen einer Impedanz zwischen den Elektroden zum Bestimmen einer modulierten Impedanz aufgrund dessen, dass ein Zielanalyt in der Probe, die in den Vertiefungen aufgenommen wird, vorliegt, wobei die modulierte Impedanz indikativ für die Konzentration des Zielanalyten in der Probe ist.
- Verfahren nach Anspruch 9, wobei das Messen der modulierten Impedanz das Anlegen einer elektrischen Spannung an die Elektroden beinhaltet.
- Verfahren nach Anspruch 9, welches ferner das Binden des Analyten im Inneren der Vertiefungen umfasst.
- Verfahren nach Anspruch 9, wobei mehrere Sensoren vorgesehen sind, wobei Abschnitte der Sensoren durch eine Schutzschicht (30, 130, 425, 530) bedeckt sind, und welches ferner das selektive Wegschmelzen der Schutzschicht zum sequentiellen Offenlegen der Abschnitte der Sensoren zum kontinuierlichen Überwachen des Analyten umfasst.
- Verfahren nach Anspruch 12, wobei die Schutzschicht eine Membran (425) ist und wobei das selektive Wegschmelzen der Membran das Anlegen einer Spannung an einen Abschnitt der Membran, um zu veranlassen, dass dieser Abschnitt der Membran schmilzt, das Überwachen einer Impedanz von einem der Sensoren, der durch die Membran bedeckt ist, und das Stoppen des Anlegens der Spannung, wenn ein Abfall der Impedanz des Sensors erkannt wird, beinhaltet.
- Transkutaner Impedanzsensor zum markierungsfreien In-situ-Nachweis eines Zielanalyten, wobei der Sensor Folgendes umfasst:a) einen Sensor nach Anspruch 1, wobei die leitenden Elektroden durch ein flexibles Substrat getragen werden, undb) eine Einführungsvorrichtung (134) zum Einführen des flexiblen Sensors durch die Haut in einen biologischen Körper.
- Sensor nach Anspruch 14, wobei die Einführungsvorrichtung (134) eine nadelförmige Spitze beinhaltet, wobei die Einführungsvorrichtung und der flexible Sensor zusammenwirken, um die Anordnung von Vertiefungen nahe der nadelförmigen Spitze zu positionieren.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762575254P | 2017-10-20 | 2017-10-20 | |
| PCT/US2018/056718 WO2019190596A1 (en) | 2017-10-20 | 2018-10-19 | Transcutaneous wearable apparatus for continuous monitoring of biomarkers in blood |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP3697303A1 EP3697303A1 (de) | 2020-08-26 |
| EP3697303B1 true EP3697303B1 (de) | 2023-03-08 |
Family
ID=67439306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP18903032.3A Active EP3697303B1 (de) | 2017-10-20 | 2018-10-19 | Transkutane tragbare vorrichtung zur kontinuierlichen überwachung von biomarkern im blut |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US20200261907A1 (de) |
| EP (1) | EP3697303B1 (de) |
| WO (1) | WO2019190596A1 (de) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020069565A1 (en) * | 2018-10-02 | 2020-04-09 | WearOptimo Pty Ltd | Measurement system |
| US11624050B2 (en) * | 2019-08-21 | 2023-04-11 | Board Of Regents, The University Of Texas System | Microneedle array electroporation system for cell transfection |
| CN111551714B (zh) * | 2020-05-18 | 2023-08-08 | 天津博奥赛斯生物科技股份有限公司 | 一种新型冠状病毒IgM抗体荧光免疫法检测试剂盒 |
| CN116547537A (zh) * | 2020-07-29 | 2023-08-04 | 皮克托有限公司 | SARS-CoV-2抗体免疫测定 |
| PL436257A1 (pl) * | 2020-12-07 | 2021-09-06 | Advanced Diagnostic Equipment Spółka Z Ograniczoną Odpowiedzialnością | Czujnik biologiczny do wykrywania białek wirusów oraz urządzenie do wykrywania białek wirusów |
| US11513097B1 (en) | 2021-05-21 | 2022-11-29 | PERSOWN, Inc. | Methods of obtaining and using electrochemical diagnostic results |
| CN113655101A (zh) * | 2021-07-23 | 2021-11-16 | 山东师范大学 | 一种电化学生物传感器及其制备方法和应用 |
| WO2023056458A1 (en) * | 2021-10-01 | 2023-04-06 | Rutgers, The State University Of New Jersey | Wireless power-up and readout of label-free electronic detection of protein biomarkers |
| WO2023135486A2 (en) * | 2022-01-13 | 2023-07-20 | Qulab Medical Ltd. | Sensing system and method using galvanic separation |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5846708A (en) * | 1991-11-19 | 1998-12-08 | Massachusetts Institiute Of Technology | Optical and electrical methods and apparatus for molecule detection |
| GB0030929D0 (en) * | 2000-12-19 | 2001-01-31 | Inverness Medical Ltd | Analyte measurement |
| EP2420824B1 (de) * | 2001-06-29 | 2018-11-28 | Meso Scale Technologies LLC | Multiwell-Platte mit einer Reihe von Wells und Kit für den Einsatz bei der Durchführung eines ECL-Assays |
| US9234867B2 (en) * | 2003-05-16 | 2016-01-12 | Nanomix, Inc. | Electrochemical nanosensors for biomolecule detection |
| US10722132B2 (en) * | 2010-12-28 | 2020-07-28 | Sotera Wireless, Inc. | Body-worn system for continuous, noninvasive measurement of cardiac output, stroke volume, cardiac power, and blood pressure |
| EP2682745B1 (de) * | 2012-07-06 | 2019-05-15 | Stichting IMEC Nederland | Überwachung von Flüssigkeitsgehalt |
| TWI486584B (zh) | 2012-11-23 | 2015-06-01 | Univ Nat Chi Nan | Electric resistance type biosensor and its manufacturing method |
| WO2016100325A1 (en) * | 2014-12-15 | 2016-06-23 | Virginia Tech Intellectual Properties, Inc. | Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment |
| WO2017062591A1 (en) | 2015-10-07 | 2017-04-13 | The University Of Toledo | A biosensor device to detect target analytes in situ, in vivo, and/or in real time, and methods of making and using the same |
-
2018
- 2018-10-19 EP EP18903032.3A patent/EP3697303B1/de active Active
- 2018-10-19 WO PCT/US2018/056718 patent/WO2019190596A1/en unknown
-
2020
- 2020-04-17 US US16/852,113 patent/US20200261907A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019190596A9 (en) | 2019-11-28 |
| US20200261907A1 (en) | 2020-08-20 |
| WO2019190596A1 (en) | 2019-10-03 |
| EP3697303A1 (de) | 2020-08-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3697303B1 (de) | Transkutane tragbare vorrichtung zur kontinuierlichen überwachung von biomarkern im blut | |
| US9316608B2 (en) | Method and apparatus for target detection using electrode-bound viruses | |
| KR101709762B1 (ko) | 생체분자 농축 기능 일체형 센서 및 그 제조방법 | |
| US20170067889A1 (en) | Lateral Flow Diagnostic Devices with Integrated Electronic Components and Methods of Use Thereof | |
| CA2879831C (en) | In vivo aptamer-based biosensor | |
| KR102657461B1 (ko) | 단일-세포 세포내 나노-ｐｈ 프로브 | |
| WO2009097174A2 (en) | Electrochemical biosensor | |
| CN110988081A (zh) | 诊断结核病的方法 | |
| Dias et al. | Electronic tongues and aptasensors | |
| US11536721B2 (en) | Electrochemical immunosensors | |
| KR20160090661A (ko) | 모세관을 이용한 단백질 농축 장치 및 이를 이용한 농축 방법 | |
| US20210114023A1 (en) | Detection system and method for producing same | |
| US20160178649A1 (en) | Method and system for sensing and detecting a target molecule | |
| KR101789043B1 (ko) | 종이접기를 통한 생체 시료 농축 장치 | |
| KR20170082843A (ko) | 생체분자 농축 장치 | |
| US20230073771A1 (en) | System and method for label-free single molecule detection | |
| WO2017053975A1 (en) | Sensor for detection of analytes | |
| Song et al. | Microwell-array on a flexible needle: A transcutaneous insertable impedance sensor for label-free cytokine detection | |
| CN114175194A (zh) | 用于传感器、电化学和能量存储的碳纳米管微电极 | |
| US20190317089A1 (en) | Multi-array impedimetric biosensors for the detection of concussion and traumatic brain injuries | |
| EP3851855A1 (de) | Abtastung von molekülen durch elektrochemische detektion von nanopartikeln | |
| JPWO2021062475A5 (de) | ||
| WO2023064235A1 (en) | Novel two electrode-based correction approach for elimination of biofouling from label-free affinity biosensors for detection | |
| Beech et al. | Biofluid sensing devices with integrative eab biosensors | |
| Chen et al. | Microelectrodes integrated cell-chip for drug effects study |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: UNKNOWN |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
| 17P | Request for examination filed |
Effective date: 20200515 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
| AX | Request for extension of the european patent |
Extension state: BA ME |
|
| DAV | Request for validation of the european patent (deleted) | ||
| DAX | Request for extension of the european patent (deleted) | ||
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
| 17Q | First examination report despatched |
Effective date: 20210326 |
|
| GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: GRANT OF PATENT IS INTENDED |
|
| INTG | Intention to grant announced |
Effective date: 20220929 |
|
| GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE PATENT HAS BEEN GRANTED |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP Ref country code: AT Ref legal event code: REF Ref document number: 1552023 Country of ref document: AT Kind code of ref document: T Effective date: 20230315 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602018047130 Country of ref document: DE |
|
| REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG9D |
|
| REG | Reference to a national code |
Ref country code: NL Ref legal event code: MP Effective date: 20230308 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: RS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: NO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230608 Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: ES Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 |
|
| P01 | Opt-out of the competence of the unified patent court (upc) registered |
Effective date: 20230628 |
|
| REG | Reference to a national code |
Ref country code: AT Ref legal event code: MK05 Ref document number: 1552023 Country of ref document: AT Kind code of ref document: T Effective date: 20230308 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: NL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230609 Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SM Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230710 Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: AT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20230918 Year of fee payment: 6 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230708 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20230918 Year of fee payment: 6 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602018047130 Country of ref document: DE |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 Ref country code: DK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20230308 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20230919 Year of fee payment: 6 |
|
| 26N | No opposition filed |
Effective date: 20231211 |